β2-glycoprotein I–dependent lupus anticoagulant highly correlates with thrombosis in the antiphospholipid syndrome
Open accessAbstract
The antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies in plasma of patients with thromboembolic complications. A major problem in defining the syndrome is that serologic assays to detect antiphospholipid antibodies have a low specificity. We recently published a method that specifically detects lupus anticoagulant (LAC) caused by anti–β2-glycoprotein I antibodies. Here, we studied the clinical relevance of detecting β2-glycoprotein I–dependent LAC. Plasma samples were collected from 198 patients with autoimmune diseases. In those samples with a positive partial thromboplastin time–lupus anticoagulant (PTT-LA), a modified activated partial thromboplastin time (aPTT)–based LAC test was performed with cardiolipin as confirming agent. Twenty-five of 58 patients with an aPTT-based LAC were dependent on the presence of anti–β2-glycoprotein I antibodies. Presence of β2-glycoprotein I–dependent LAC was almost completely associated with a history of thromboembolic complications (odds ratio, 42.3; 95% confidence interval, 194.3-9.9). An increased frequency of thrombosis was not found in 33 patients with LAC independent of anti–β2-glycoprotein I antibodies (odds ratio, 1.6; 95% confidence interval, 3.9-0.8). The use of an LAC assay with cardiolipin as confirming agent strongly improves the detection of patients at risk of thrombosis. Our findings suggest that anti–β2-glycoprotein I antibodies with LAC activity are antibodies that are responsible for the thromboembolic complications in the antiphospholipid syndrome.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
These results confirm and validate several previous reports that have implicated these antibodies in the pathogenesis of APS.
“These results confirm and validate several previous reports that have implicated these antibodies in the pathogenesis of APS [9, 10, 12, 13, 29, 30], but they also add to the growing body of evidence that shows inconsistent associations between aPL-associated autoantibodies and anamnestic thrombotic risk [3, 16].”
From Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant (2017) · cites this paper as [13]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Galli, M., Luciani, D., Bertolini, G., & Barbui, T. (2003) · Blood · doi:10.1182/blood-2002-02-0441 · Cited by 974 · see citing works
Thrombosis, abortion, cerebral disease, and the lupus anticoagulant.
Hughes, G. R. V. (1983) · BMJ · doi:10.1136/bmj.287.6399.1088 · Cited by 958 · see citing works
Galli, M., Luciani, D., Bertolini, G., & Barbui, T. (2003) · Blood · doi:10.1182/blood-2002-11-3334 · Cited by 413 · see citing works
Horbach, D. A., van Oort, E., Donders, R. C. J. M., Derksen, R. H. W. M., & de Groot, P. G. (1996) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1650686 · Cited by 246 · see citing works
Self-citationBrandt, J. T., Barna, L. K., & Triplett, D. A. (1995) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1649988 · Cited by 231 · see citing works
Isolation and characterization of bovine factor IX (Christmas factor)
Fujikawa, K., Thompson, A. R., Legaz, M. E., et al. (1973) · Biochemistry · doi:10.1021/bi00748a019 · Cited by 208 · see citing works
Immunological specificity and mechanism of action of IgG lupus anticoagulants
Pengo, V., Thiagarajan, P., Shapiro, S., & Heine, M. (1987) · Blood · doi:10.1182/blood.v70.1.69.69 · Cited by 194 · see citing works
Blank, M., Shoenfeld, Y., Cabilly, S., Heldman, Y., Fridkin, M., & Katchalski‐Katzir, E. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.9.5164 · Cited by 180 · see citing works
Jankowski, M., Vreys, I., Wittevrongel, C., Boon, D., Vermylen, J., Hoylaerts, M., & Arnout, J. (2002) · Blood · doi:10.1182/blood-2002-05-1310 · Cited by 175 · see citing works
Iverson, G. M., Reddel, S., Victoria, E. J., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.12.7097 · Cited by 146 · see citing works
Forastiero, R. R., Martinuzzo, M. E., Cerrato, G. S., Kordich, L., & Carreras, L. O. (1997) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1657678 · Cited by 146 · see citing works
Derksen, R. H. W. M., Hasselaar, P., Blokzijl, L., Gmelig-Meyling, F. H. J., & de Groot, P. G. (1988) · Annals of the Rheumatic Diseases · doi:10.1136/ard.47.5.364 · Cited by 138 · see citing works
Self-citationArnout, J., & Vermylen, J. (2003) · Journal of Thrombosis and Haemostasis · doi:10.1046/j.1538-7836.2003.00125.x · Cited by 107 · see citing works
Simmelink, M. J. A., Derksen, R. H. W. M., Arnout, J., & de Groot, P. G. (2003) · Journal of Thrombosis and Haemostasis · doi:10.1046/j.1538-7836.2003.00146.x · Cited by 77 · see citing works
Self-citationHeterogeneity and Immunochemical Properties of Anti-β2-glycoprotein I Autoantibodies
Regnault, V., HACHULLA, E., Darnige, L., et al. (1998) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1615218 · Cited by 44 · see citing works
Blank, M., Waisman, A., Mozes, E., et al. (1999) · International Immunology · doi:10.1093/intimm/11.12.1917 · Cited by 35 · see citing works
Update on antiphospholipid antibodies
Roubey, R. A. S. (2000) · Current Opinion in Rheumatology · doi:10.1097/00002281-200009000-00004 · Cited by 33 · see citing works
Lupus anticoagulant in cardiovascular diseases: the role of beta2-glycoprotein I.
Groot, P. G. D., Bouma, B. J., Lutters, B. C., et al. (2000) · PubMed · Cited by 9 · see citing works
Wilson (1999) · doi:10.1002/1529-0131(199907)42:7
Flagged first, then by citations
Research works printed but not linked: 2
- Roubey RA. Update on antiphospholipid antibod- ies. Curr Opin Rheumatol. 2000;12:374-378.
- Iverson GM, Reddel S, Victoria EJ, et al. Use of singlepoint mutations in domain I of b2-glycopro- tein I to determine fine antigenic specificity of an- tiphospholipid autoantibodies. J Immunol. 2002; 169:7079-7103.
Cited by
Sorted by citations
MIYAKIS, S., LOCKSHIN, M. D., ATSUMI, T., BRANCH, D. W., BREY, R. L., CERVERA, R., DERKSEN, R. H. W. M., DE GROOT, P. G., KOIKE, T., MERONI, P. L., et al. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.01753.x · Cited by 7,203 · see citing works
Self-citationGuidelines on the investigation and management of antiphospholipid syndrome
Keeling, D., Mackie, I., Moore, G. W., Greer, I. A., Greaves, M., & British Committee for Standards in Haematology (2012) · British Journal of Haematology · doi:10.1111/j.1365-2141.2012.09037.x · Cited by 740 · see citing works
Urbanus, R. T., Siegerink, B., Roest, M., Rosendaal, F. R., de Groot, P. G., & Algra, A. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70239-x · Cited by 429 · see citing works
Self-citationde Laat, B., Derksen, R. H. W. M., Urbanus, R. T., & de Groot, P. G. (2005) · Blood · doi:10.1182/blood-2004-09-3387 · Cited by 378 · see citing works
Self-citationDE LAAT, B., PENGO, V., PABINGER, I., MUSIAL, J., VOSKUYL, A. E., BULTINK, I. E. M., RUFFATTI, A., ROZMAN, B., KVEDER, T., DE MOERLOOSE, P., et al. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03588.x · Cited by 291 · see citing works
Self-citationRand, J. H., Wu, X.-X., Quinn, A. S., Chen, P. P., Hathcock, J. J., & Taatjes, D. J. (2008) · Blood · doi:10.1182/blood-2008-03-144204 · Cited by 215 · see citing works
Galli, M., Borrelli, G., Jacobsen, E. M., Marfisi, R. M., Finazzi, G., Marchioli, R., Wisloff, F., Marziali, S., Morboeuf, O., & Barbui, T. (2007) · Blood · doi:10.1182/blood-2007-01-066043 · Cited by 170 · see citing works
Pengo, V., Ruffatti, A., Tonello, M., Cuffaro, S., Banzato, A., Bison, E., Denas, G., & Padayattil Jose, S. (2015) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12865 · Cited by 126 · see citing works
de Laat, B., Wu, X.-X., van Lummel, M., Derksen, R. H. W. M., de Groot, P. G., & Rand, J. H. (2007) · Blood · doi:10.1182/blood-2006-07-030148 · Cited by 122 · see citing works
Self-citationAntiphospholipid antibody testing and standardization
Devreese, K. M. J. (2014) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12234 · Cited by 98 · see citing works
Incidence of a first thromboembolic event in carriers of isolated lupus anticoagulant
Pengo, V., Testa, S., Martinelli, I., Ghirarduzzi, A., Legnani, C., Gresele, P., Passamonti, S. M., Bison, E., Denas, G., Jose, S. P., et al. (2015) · Thrombosis Research · doi:10.1016/j.thromres.2014.10.013 · Cited by 89 · see citing works
Invitation to a debate on the serological criteria that define the antiphospholipid syndrome
GALLI, M., REBER, G., DE MOERLOOSE, P., & DE GROOT, P. G. (2008) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2008.02862.x · Cited by 85 · see citing works
Self-citationThe antiphospholipid syndrome: still an enigma
Chaturvedi, S., & McCrae, K. R. (2015) · Hematology · doi:10.1182/asheducation-2015.1.53 · Cited by 51 · see citing works
IgA antiphospholipid antibodies are an independent risk factor for thromboses
Shen, Y., Lee, R., Frenkel, E., & Sarode, R. (2008) · Lupus · doi:10.1177/0961203308093460 · Cited by 39 · see citing works
Du, V. X., Kelchtermans, H., de Groot, P. G., & de Laat, B. (2013) · Thrombosis Research · doi:10.1016/j.thromres.2013.07.023 · Cited by 35 · see citing works
Self-citationPosch, F., Gebhart, J., Rand, J. H., Koder, S., Quehenberger, P., Pengo, V., Ay, C., & Pabinger, I. (2017) · BMC Medicine · doi:10.1186/s12916-017-0807-7 · Cited by 25 · see citing works
“Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, de Groot PG, Koike T, Meroni PL, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).”
ResultInfluentialViewpoint: Lupus anticoagulant detection and interpretation in antiphospholipid syndrome
Efthymiou, M., Bertolaccini, M. L., & Cohen, H. (2024) · Rheumatology · doi:10.1093/rheumatology/kead623 · Cited by 5 · see citing works
- Authors
- de Laat, H. B., Derksen, R. H. W. M., Urbanus, R. T., Roest, M., & de Groot, P. G.
- Affiliations
- From the Department of Haematology, University Medical Centre Utrecht, the Netherlands; the Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, the Netherlands; and the Department of Clinical Chemistry, University Medical Centre Utrecht, the Netherlands.
- University Medical Center Utrecht (NL)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2004-12-01
- Volume
- 104
- Issue
- 12
- Pages
- 3598-3602
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1596249994
- Cited by
- 219
- References
- 19
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 8 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 11 · 2018: 4 · 2017: 12 · 2016: 14 · 2015: 8 · 2014: 15 · 2013: 11 · 2012: 7
- FWCI
- 9.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Keywords
- antiphospholipid syndrome, lupus anticoagulant, beta2-glycoprotein I, anti-beta2-glycoprotein I antibodies, thrombosis, thromboembolic events, cardiolipin, antiphospholipid antibodies, activated partial thromboplastin time, autoimmune disease
- MeSH terms
- Adult, Autoantibodies, Female, Glycoproteins, Humans, Male, Partial Thromboplastin Time, Predictive Value of Tests, Retrospective Studies, Thrombosis, Odds Ratio, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, beta 2-Glycoprotein I
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
